The objective of the research is synthesis and avaluation of new compounds as potentially non-addicting analgesic agents. The approach is based on modification of existing opiate congeners with computerized calculation of conformational and electronic properties of analogs and correlation of results with observed behavior in bioassay systems. During the project year effort was continued in the N-sec-alkyl morphinoids, particularly separation of diastereomeric forms and comparison of biological data between R and S configurational isomers. Current effort is devoted to C-9-C-16 alkyl morphinoids and measurement of antagonist potencies of compounds prepared to date. BIBLIOGRAPHIC REFERENCES: An improved method for O-demethylation of codeine. J. A. Lawson and J. I. DeGraw. J. Med. Chem. 20, 165 (1977). Bioassay of N-sec-butylmorphine and N-alpha-methylnalorphine. E.T. Uyeno, J.I. DeGraw, H.L. Johnson, J.A. Lawson and G. Loew. Proc. Western Pharmacol. Soc. 20, 1977, abstract.